Abstract: The objective of this project is to develop a new label-free sensing modality capable of detecting and quantifying DNA methylation. The sensor platform is based on a rare- earth doped optical cavity, which forms a nanolaser, in combination with a receptor- based surface functionalization. This optical sensor, which can perform detection in either the optical or electrical domain, will be developed to detect and to quantify CpG methylation at multiple sites in DNA sequences without the use of PCR. Its application to early ovarian cancer detection and monitoring will be demonstrated with the detection of multiple CpG methylation sites in RASS F1A and BRCA1. Analysis of epigenetic markers in peripheral blood and tumor tissue has shown promise in the early detection, prognosis, and treatment of cancer. However, the analysis of these markers is hampered by the lack of sensitivity, specificity, and reproducibility of current detection techniques. This proposed research will develop a completely novel sensor platform with unprecedented capabilities for detecting epigenetic changes, and applies it to early ovarian cancer detection and monitoring, and to studying the fundamental underlying mechanisms of cancer progression. Current techniques to screen for ovarian cancer using single serum protein biomarkers have not been successful. However, there is growing evidence that use of multiple markers will have utility for screening and monitoring therapeutic efficacy. Previous nanosensor research by the PI has resulted in the development of label-free, single protein molecule sensing techniques based on optical resonant cavities which function in both buffer and serum. It is proposed that the nanolaser sensor will be useful in detecting epigenetic changes in serum DNA, providing a universal platform for detecting and monitoring ovarian cancer utilizing both protein and epigenetic changes. Public Health Relevance: Analysis of epigenetic markers in peripheral blood and tumor tissue has shown promise in the early detection, prognosis, and treatment of ovarian cancer;however, the analysis of these markers is hampered by the lack of sensitivity, specificity, and reproducibility of current detection techniques. Our goal is to develop a new sensing modality capable of detecting and characterizing epigenetic markers for ovarian cancer and to develop it for studying the frequency of epigenetic events. As a result of the improved performance, the heterodyned nanolaser sensor will be able to detect and to quantify cancer associated methylation, specifically CpG methylation sites in the RASSF1A and BRCA1 promoters.